akn
Musclechemistry Member
In order to develop products that would be effective
therapeutically, chemists needed to solve a number of
problems with using natural steroid hormones for
treatment. For example, oral dosing was a problem, as our
basic steroids testosterone, nandrolone, and
dihydrotestosterone are ineffective when administered
this way. The liver would efficiently break down their
structure before reaching circulation, so some form of
alteration was required in order for a tablet or capsule to
be produced. Our natural steroid hormones also have very
short half-lives in the body, so when administered by
injection, an extremely frequent and uncomfortable
dosing schedule is required if a steady blood level is to be
achieved.Therefore, extending steroid activity was a major
goal for many chemists during the early years of synthetic
AAS development. Scientists also focused on the nagging
problems of possible excess estrogenic buildup in the
blood, particularly with testosterone, which can become
very uncomfortable for patients undergoing therapy.
Methylated Compounds and Oral Dosing
Chemists realized that by replacing the hydrogen atom at
the steroid's 17th alpha position with a carbon atom (a
process referred to as alkylation), its structure would be
notably resistant to breakdown by the liver. The carbon
atom is typically added in the form of a methyl group
(CH3), although we see oral steroids with an added ethyl(C2HS) grouping as well. A steroid with this alteration is
commonly described as a C-17 alpha alkylated oral,
although the terms methylated or ethylated oral steroid
are also used. The alkyl group cannot be removed
metabolically, and therefore inhibits reduction of the
steroid to its inactive 17-ketosteroid form by occupying
one of the necessary carbon bonds. Before long,
pharmaceutical companies had utilized this advance (and
others) to manufacture an array of effective oral steroids
including methyltestosterone, Dianabol, Winstrol®,Anadrol SO®, Halotestin®, Nilevar, Orabolin, and Anavar.
The principle drawback to these compounds is that they
place a notable amount of stress on the liver, which in
some instances can lead to actual damage to this organ.
Because the alkyl group cannot be removed, it mediates
the action of the steroid in the body. Methyltestosterone,
for example, is not simply an oral equivalent of
testosterone, as the added alkylation changes the activity
of this steroid considerably. One major change we see is
an increased tendency for the steroid to produce
estrogenic· side effects, despite the fact that it actually
lowers the ability of the hormone to interact with
aromatase.45 Apparently with 17-alkylation present on a
steroid, aromatization (when possible) produces a more
active form of estrogen (typically 17alpha-methyl or
17alpha-ethyl estradiol). These estrogens are more
biologically active than estradiol due to their longer halflife
and weaker tendency to bind with serum proteins. In
some instances, 17alpha-alkylation will also enhance the
ability of the initial steroid compound to bind with and
activate the estrogen or progesterone receptor.46 An
enhancement of estrogenic properties is also obvious
when we look at methandrostenolone, which is an
alkylated form of boldenone (Equipoise®), and Nilevar,
which is an alkylated form of the mild anabolic
nandrolone. Dianabol is clearly more estrogenic than
Equipoise®, a drug not noted for producing strong side effects of this nature. The same holds true for the
comparison of Nilevar to Deca-Durabolin, a compound
that we also know to be extremely mild in this regard.
C17 alpha alkylation also typically lowers the affinity in
which the steroid binds to the androgen receptor, as is
noted with the weak relative binding affinity of such
popular agents as Dianabol and Winstrol (stanozolol).
However, since this alteration also greatly prolongs the
half-life of a steroid, as well as increases the tendency for it to exist in an unbound state, it creates a more potent
anabolic/androgenic agent in both cases. This explains
why Dianabol and stanozolol are notably effective in
relatively lower weekly doses (often 140 mg weekly will
produce notable growth) compared to injectables such as
testosterone and nandrolone, which often need to reach
doses of 300-400 mg weekly for a similar level of effect.
non-Alkylated Orals
In an attempt to solve the mentioned problems with liver
toxicity we see with c17-alpha alkylated compounds, a
number of other orals with different chemical alterations
(such as Primobolan®, Proviron®, AndriolE, and
Anabolicum Vister) were created. Primobolan® and
Proviron® are alkylated at the one position (methyl), a trait
which also slows ketosteroid reduction. Andriol® uses a
17beta carboxylic acid ester (used with injectable
compounds, discussed below), however, here the oildissolved
steroid is sealed in a capsule and is intended for
oral administration. This is supposed to promote steroid
absorption through intestinal lymphatic ducts, bypassing
the first pass through the liver. In addition to 1
methylation, Primobolan® also utilizes a 17 beta ester
(acetate) to further protect against reduction to inactive
form (here there is no lymphatic system absorption).
Anabolicum Vister uses 17beta enol ether linkage to
protect the steroid, which is very similar to esterification as
the ether breaks off to release a steroid base (boldenone
in this case). While all of these types of compounds do not
place the same stress on the liver, they are also much less
resistant to breakdown than 17 alkylated orals, and are
ultimately less active milligram for milligram.
Esters and Injectable Compounds
You may notice that many injectable steroids will list long
chemical names like testosterone cypionate and
testosterone enanthate, instead of just testosterone. In
these cases, the cypionate and enanthate are esters
(carboxylic acids) that have been attached to the 17-beta
hydroxyl group of the testosterone molecule, which increase the active life span of the steroid preparation.
Such alterations will reduce the steroid's level of water
solubility, and increase its oil solubility. Once an esterified
compound has been injected, it will form a deposit in the
l'Tluscle tissue (depot) from which it will slowly enter
circulation. Generally the larger the ester chain, the more
oil soluble the steroid compound will be, and the longer it
will take for the full dosage to be released. Once free in
circulation, enzymes will quickly remove the ester chain
and the parent hormone will be free to exert its activity
(while the ester is present the steroid is inert).
There are a wide number of esters, which can provide
varying release times, used in medicine today.To compare,
an ester like decanoate can extend the release of active
parent drug into the blood stream for three to four weeks,
while it may only be extended for a few days with an
acetate or propionate ester. The use of an ester allows for
a much less frequent injection schedule than if using a
water-based (straight) testosterone, which is much more
comfortable for the patient. We must remember when
calculating dosages, that the ester is figured into the
steroid's measured weight. 100 mg of testosterone
enanthate, therefore, contains much less base hormone
than 100 mg of a straight testosterone suspension (in this
case it equals 72mg of testosterone). In some instances, an
ester may account for roughly 40% or more of the total
steroid weight, but the typical measure is somewhere
around 15% to 350/0. Below are the free base equivalents
for several popular steroid compounds.
It is also important to stress the fact that esters do not
alter the activity of the parent steroid in any way. They
work only to slow its release. It is quite common to hear
people speak about the properties of different esters,
almost as if they can magically alter a steroid's
effectiveness. This is really nonsense. Enanthate is not
more powerful than cypionate (perhaps a few extra
milligrams of testosterone released per injection, but
nothing to note), nor is Sustanon some type of incredible
testosterone blend. Personally, I have always considered
Sustanon a very poor buy in the face of cheaper 250 mg enanthate ampules. Your muscle cells see only
testosterone; ultimately there is no difference. Reports of
varying levels of muscle gain, androgenic side effects,
water retention, etc. are only issues of timing. Fasterreleasing
testosterone esters will produce estrogen
buildup faster simply because there is more testosterone
free in the blood from the start of the cycle. The same is
true when we state that Durabolin® is a milder
nandrolone for women compared to Deca. It is simply
easier to control the blood level with a faster acting drug.
Were virilization symptoms to become apparent,
hormone levels will drop much faster once we stop
administration. This should not be confused with the
notion that the nandrolone in Durabolin® acts differently
in the body than that released from a shot of DecaDurabolin
®.
It is also worth noting that while the ester is typically
hydrolyzed in general circulation, some will be hydrolyzed
at the injection site where the steroid depot first contacts
blood. This will cause a slightly higher concentration of
both free steroid and ester in the muscle where the drug
had been administered. On the plus side, this may equate
to slightly better growth in this muscle, as more hormone
is made available to nearby cells. Many bodybuilders have
come to swear by the use of injection sites such as the
deltoids, biceps, and triceps, truly believing better growth
can be achieved if the steroid is injected directly into
these muscles. The negative to this is that the ester itself
may be irritating to the tissues at the site of injection once
it is broken free. In some instances it can be so caustic that
the muscle itself will become swollen and sore due to the
presence of the ester, and the user may even suffer a lowgrade
fever as the body fights off the irritant (the onset of
such symptoms typically occurs 24-72 hours after
injection). This effect is more common with small chain
esters such as propionate and acetate, and can actually
make a popular steroid such as Sustanon (which contains
testosterone propionate) off-limits for some users who
experience too much discomfort to justify using the drug.
Longer chain esters such as decanoate and cypionate are
typically much less irritating at the site of injection, and
therefore are preferred by sensitive individuals.
AnaboliclAndrogenic Dissociation
Although never complete, scientists had some success in
their quest to separate the androgenic and anabolic
properties of testosterone. A number of synthetic
anabolic steroids had been developed as a result, with
many being notably weaker and stronger than our base
androgen. In order to first assess the anabolic and
androgenic potential of each newly developed steroid,
scientists had generally used rats as a model. To judge
androgenic potency the typical procedure involved the post-administration measure (0/0 growth) of the seminal
vesicles and ventral prostate. These two tissues will often
respond unequally to a given steroid, however, so an
average of the two figures is used. Anabolic activity was
most commonly determined by measuring the growth of
the levator ani, a sex organ (not skeletal) muscle. This
tissue may not be the most ideal one to use though, as it
contains more androgen receptor than most skeletal
muscles (the AR is still less abundant here than in target
tissues such as the ventral prostate).47 48 In integrating
both measures, the anabolic index is used, which relates
the ratio of anabolic to androgenic response for a given
steroid. An anabolic index greater than one indicates a
higher tendency for anabolic effect, and therefore
classifies the drug as an anabolic steroid. A measure lower
than one in turn assesses the steroid as androgenic. There
is some variance between experimental results and the
actual real world experiences with humans, but (with a
few exceptions) designations based on the anabolic index
are generally accepted. Below are discussed a few factors
that greatly affect anabolic/androgenic dissociation.
Nandrolone and 19-norandrogens
The section of this book dealing with DHT conversion is
important, because it helps us understand the anabolic
steroid nandrolone and many of its derivatives.
Nandrolone is identical to testosterone except it lacks a
carbon atom in the 19th position, hence its other given
name 19-nortestosterone. Nandrolone is very interesting
because it offers the greatest ratio of anabolic to
androgenic effect of the three natural steroids (see:
Synthetic AAS Chemistry).This is because it is metabolized
into a less potent structure (dihydronandrolone) in
androgen target tissues with high concentrations of the 5alpha
reductase enzyme, which is the exact opposite of
what happens with testosterone. Apparently the removal
of the c4-5 double bond, which normally increases the
androgen receptor binding capability of testosterone,
causes an unusual lowering of this ability with
nandrolone.lnstead of becoming three to four times more
potent, it becomes several times weaker. This is a very
desirable trait if you want to target anabolic effects over
androgenic. This characteristic also carries over to most
synthetic steroids derived from nandrolone, making this
an attractive base steroid to use in the synthesis of new,
primarily anabolic, steroids.
5-alpha Irreducible Steroids
When we look at the other mild anabolic steroids
Primobolan®, Winstrol®, and Anavar, none of which are
derived from nandrolone, we see another interesting
commonality. These steroids are DHT derivatives that are unaffected by 5alpha-reductase, and therefore become neither weaker nor
stronger in androgen responsive target tissues with high concentrations of this
enzyme. In essence, they have a very balanced effect between muscle and
androgen tissues, making them outwardly less androgenic than testosterone.
This is why these steroids are technically classified as anabolics, and are
undeniably less troublesome than many other steroids in terms of promoting
androgenic side effects. However, if we wanted to look for the absolute least
androgenic steroid, the title would still go to nandrolone (or perhaps one of its
derivatives). Female bodybuilders should likewise take note that despite the
recommendations of others, steroids like Anavar, Winstrol and Primo are not
the least risky steroids to use. This is of great importance, as male sex
hormones can produce many undesirable and permanent side effects when
incorrectly taken by females (See: Side Effects, Virilization).
3-alpha Hydroxysteroid Dehydrogenase
The 3-alpha hydroxysteroid dehydrogenase enzyme is also important,
because it can work to reduce the anabolic potency of certain steroids
considerably. As follows, not all potent binders of the androgen receptor are,
as a rule, great muscle-building drugs, and this enzyme is an important factor.
Dihydrotestosterone is a clear example. Just as the body converts
testosterone to DHT as a way to potentiate its action in certain tissues (skin,
scalp, prostate, etc.), it also has ways of countering the strong activity of
DHT, in other tissues where it is unneeded. This is accomplished by the
rapid reduction of DHT to its inactive active metabolites, namely
androstanediol, before it reaches the androgen receptor. This activity occurs
via interaction with the 3-alpha hydroxysteroid dehydrogenase enzyme. This
enzyme is present in high concentrations in certain tissues, including skeletal
muscle, and DHT is much more open to alteration by it than other steroids
that possess a c4-5 double-bond (like testosterone).49 This causes
dihydrotestosterone to be an extremely poor anabolic, despite the fact that it
actually exhibits a much higher affinity for the cellular androgen receptor than
most other steroids. Were it able to reach the cellular androgen receptor
without first being metabolized by 3a-HSD, it certainly would be a
formidable muscle-building steroid. Unfortunately this is not the case,
explaining why injectable dihydrotestosterone preparations (no longer
commercially produced) were never favorite drugs among athletes looking to
build mass. This trait is also shared by the currently popular oral androgen
Proviron®, which is, in essence, just an oral form of DHT (1-methyldihydrotestosterone to be specific) and known to be an extremely poor tissue
builder.
Anabolics and Potency
One must remember that being classified as an anabolic just means that the
steroid is more inclined to produce muscle growth than androgenic side
effects. Since both effects are mediated through the same receptor, and
growth is not produced by androgen receptor activation in muscle tissue
alone (other CNS tissues, for example, are integral to this process as well),
we find that a reduction in the androgenic activity of a compound will often
coincide with a similar lowering of its muscle-building effectiveness. If we are
just looking at overall muscle growth, androgenic steroids (usually potent due
to their displaying a high affinity to bind with the androgen receptor in all
tissues) are typically much more productive muscle-builders than anabolics,
which usually bind with lower affinity in many tissues. In fact, with all of the
analogues produced throughout the years, the base androgen testosterone is
still considered to be one of the most effective bulking agents. The user must
simply endure more side effects when acquiring his or her new muscle with
this type of drug. Individuals wishing to avoid the stronger steroids will,
therefore, make a trade-off, accepting less overall muscle gain in order to run
a more comfortable cycle.
RBA Assay:
Another way of evaluating the potential ratio of anabolic to androgenic
activity is the practice of comparing the relative binding affinity (RBA) of
various steroids for the androgen receptor in rat skeletal muscle versus
prostate. When we look at the detailed study published in 1984, we see some
recognizable (and expected) trends. Aside from dihydrotestosterone and
Proviron® (mesterolone), which undergo rapid enzymatic reduction in
muscle tissue to inactive metabolites, the remaining anabolic/androgenic
steroids seem to bind with near equal affinity to receptors in both tissues.
They seem to be relatively “balanced” in effect. This study also discusses the
unique activity of testosterone and nandrolone compounds, which are good
substrates for the 5a-reductase enzyme found in androgen target tissues (such
as the prostate), and seem to provide the most notable variance between
anabolic and androgenic effect in humans due to this local metabolism. When
it comes to real-world use in humans, anabolic steroids do not always behave
in 100% uniformity with their anabolic and androgenic profiles as determined
by animal models, so all such figures need to be taken with a small grain of
salt.
therapeutically, chemists needed to solve a number of
problems with using natural steroid hormones for
treatment. For example, oral dosing was a problem, as our
basic steroids testosterone, nandrolone, and
dihydrotestosterone are ineffective when administered
this way. The liver would efficiently break down their
structure before reaching circulation, so some form of
alteration was required in order for a tablet or capsule to
be produced. Our natural steroid hormones also have very
short half-lives in the body, so when administered by
injection, an extremely frequent and uncomfortable
dosing schedule is required if a steady blood level is to be
achieved.Therefore, extending steroid activity was a major
goal for many chemists during the early years of synthetic
AAS development. Scientists also focused on the nagging
problems of possible excess estrogenic buildup in the
blood, particularly with testosterone, which can become
very uncomfortable for patients undergoing therapy.
Methylated Compounds and Oral Dosing
Chemists realized that by replacing the hydrogen atom at
the steroid's 17th alpha position with a carbon atom (a
process referred to as alkylation), its structure would be
notably resistant to breakdown by the liver. The carbon
atom is typically added in the form of a methyl group
(CH3), although we see oral steroids with an added ethyl(C2HS) grouping as well. A steroid with this alteration is
commonly described as a C-17 alpha alkylated oral,
although the terms methylated or ethylated oral steroid
are also used. The alkyl group cannot be removed
metabolically, and therefore inhibits reduction of the
steroid to its inactive 17-ketosteroid form by occupying
one of the necessary carbon bonds. Before long,
pharmaceutical companies had utilized this advance (and
others) to manufacture an array of effective oral steroids
including methyltestosterone, Dianabol, Winstrol®,Anadrol SO®, Halotestin®, Nilevar, Orabolin, and Anavar.
The principle drawback to these compounds is that they
place a notable amount of stress on the liver, which in
some instances can lead to actual damage to this organ.
Because the alkyl group cannot be removed, it mediates
the action of the steroid in the body. Methyltestosterone,
for example, is not simply an oral equivalent of
testosterone, as the added alkylation changes the activity
of this steroid considerably. One major change we see is
an increased tendency for the steroid to produce
estrogenic· side effects, despite the fact that it actually
lowers the ability of the hormone to interact with
aromatase.45 Apparently with 17-alkylation present on a
steroid, aromatization (when possible) produces a more
active form of estrogen (typically 17alpha-methyl or
17alpha-ethyl estradiol). These estrogens are more
biologically active than estradiol due to their longer halflife
and weaker tendency to bind with serum proteins. In
some instances, 17alpha-alkylation will also enhance the
ability of the initial steroid compound to bind with and
activate the estrogen or progesterone receptor.46 An
enhancement of estrogenic properties is also obvious
when we look at methandrostenolone, which is an
alkylated form of boldenone (Equipoise®), and Nilevar,
which is an alkylated form of the mild anabolic
nandrolone. Dianabol is clearly more estrogenic than
Equipoise®, a drug not noted for producing strong side effects of this nature. The same holds true for the
comparison of Nilevar to Deca-Durabolin, a compound
that we also know to be extremely mild in this regard.
C17 alpha alkylation also typically lowers the affinity in
which the steroid binds to the androgen receptor, as is
noted with the weak relative binding affinity of such
popular agents as Dianabol and Winstrol (stanozolol).
However, since this alteration also greatly prolongs the
half-life of a steroid, as well as increases the tendency for it to exist in an unbound state, it creates a more potent
anabolic/androgenic agent in both cases. This explains
why Dianabol and stanozolol are notably effective in
relatively lower weekly doses (often 140 mg weekly will
produce notable growth) compared to injectables such as
testosterone and nandrolone, which often need to reach
doses of 300-400 mg weekly for a similar level of effect.
non-Alkylated Orals
In an attempt to solve the mentioned problems with liver
toxicity we see with c17-alpha alkylated compounds, a
number of other orals with different chemical alterations
(such as Primobolan®, Proviron®, AndriolE, and
Anabolicum Vister) were created. Primobolan® and
Proviron® are alkylated at the one position (methyl), a trait
which also slows ketosteroid reduction. Andriol® uses a
17beta carboxylic acid ester (used with injectable
compounds, discussed below), however, here the oildissolved
steroid is sealed in a capsule and is intended for
oral administration. This is supposed to promote steroid
absorption through intestinal lymphatic ducts, bypassing
the first pass through the liver. In addition to 1
methylation, Primobolan® also utilizes a 17 beta ester
(acetate) to further protect against reduction to inactive
form (here there is no lymphatic system absorption).
Anabolicum Vister uses 17beta enol ether linkage to
protect the steroid, which is very similar to esterification as
the ether breaks off to release a steroid base (boldenone
in this case). While all of these types of compounds do not
place the same stress on the liver, they are also much less
resistant to breakdown than 17 alkylated orals, and are
ultimately less active milligram for milligram.
Esters and Injectable Compounds
You may notice that many injectable steroids will list long
chemical names like testosterone cypionate and
testosterone enanthate, instead of just testosterone. In
these cases, the cypionate and enanthate are esters
(carboxylic acids) that have been attached to the 17-beta
hydroxyl group of the testosterone molecule, which increase the active life span of the steroid preparation.
Such alterations will reduce the steroid's level of water
solubility, and increase its oil solubility. Once an esterified
compound has been injected, it will form a deposit in the
l'Tluscle tissue (depot) from which it will slowly enter
circulation. Generally the larger the ester chain, the more
oil soluble the steroid compound will be, and the longer it
will take for the full dosage to be released. Once free in
circulation, enzymes will quickly remove the ester chain
and the parent hormone will be free to exert its activity
(while the ester is present the steroid is inert).
There are a wide number of esters, which can provide
varying release times, used in medicine today.To compare,
an ester like decanoate can extend the release of active
parent drug into the blood stream for three to four weeks,
while it may only be extended for a few days with an
acetate or propionate ester. The use of an ester allows for
a much less frequent injection schedule than if using a
water-based (straight) testosterone, which is much more
comfortable for the patient. We must remember when
calculating dosages, that the ester is figured into the
steroid's measured weight. 100 mg of testosterone
enanthate, therefore, contains much less base hormone
than 100 mg of a straight testosterone suspension (in this
case it equals 72mg of testosterone). In some instances, an
ester may account for roughly 40% or more of the total
steroid weight, but the typical measure is somewhere
around 15% to 350/0. Below are the free base equivalents
for several popular steroid compounds.
It is also important to stress the fact that esters do not
alter the activity of the parent steroid in any way. They
work only to slow its release. It is quite common to hear
people speak about the properties of different esters,
almost as if they can magically alter a steroid's
effectiveness. This is really nonsense. Enanthate is not
more powerful than cypionate (perhaps a few extra
milligrams of testosterone released per injection, but
nothing to note), nor is Sustanon some type of incredible
testosterone blend. Personally, I have always considered
Sustanon a very poor buy in the face of cheaper 250 mg enanthate ampules. Your muscle cells see only
testosterone; ultimately there is no difference. Reports of
varying levels of muscle gain, androgenic side effects,
water retention, etc. are only issues of timing. Fasterreleasing
testosterone esters will produce estrogen
buildup faster simply because there is more testosterone
free in the blood from the start of the cycle. The same is
true when we state that Durabolin® is a milder
nandrolone for women compared to Deca. It is simply
easier to control the blood level with a faster acting drug.
Were virilization symptoms to become apparent,
hormone levels will drop much faster once we stop
administration. This should not be confused with the
notion that the nandrolone in Durabolin® acts differently
in the body than that released from a shot of DecaDurabolin
®.
It is also worth noting that while the ester is typically
hydrolyzed in general circulation, some will be hydrolyzed
at the injection site where the steroid depot first contacts
blood. This will cause a slightly higher concentration of
both free steroid and ester in the muscle where the drug
had been administered. On the plus side, this may equate
to slightly better growth in this muscle, as more hormone
is made available to nearby cells. Many bodybuilders have
come to swear by the use of injection sites such as the
deltoids, biceps, and triceps, truly believing better growth
can be achieved if the steroid is injected directly into
these muscles. The negative to this is that the ester itself
may be irritating to the tissues at the site of injection once
it is broken free. In some instances it can be so caustic that
the muscle itself will become swollen and sore due to the
presence of the ester, and the user may even suffer a lowgrade
fever as the body fights off the irritant (the onset of
such symptoms typically occurs 24-72 hours after
injection). This effect is more common with small chain
esters such as propionate and acetate, and can actually
make a popular steroid such as Sustanon (which contains
testosterone propionate) off-limits for some users who
experience too much discomfort to justify using the drug.
Longer chain esters such as decanoate and cypionate are
typically much less irritating at the site of injection, and
therefore are preferred by sensitive individuals.
AnaboliclAndrogenic Dissociation
Although never complete, scientists had some success in
their quest to separate the androgenic and anabolic
properties of testosterone. A number of synthetic
anabolic steroids had been developed as a result, with
many being notably weaker and stronger than our base
androgen. In order to first assess the anabolic and
androgenic potential of each newly developed steroid,
scientists had generally used rats as a model. To judge
androgenic potency the typical procedure involved the post-administration measure (0/0 growth) of the seminal
vesicles and ventral prostate. These two tissues will often
respond unequally to a given steroid, however, so an
average of the two figures is used. Anabolic activity was
most commonly determined by measuring the growth of
the levator ani, a sex organ (not skeletal) muscle. This
tissue may not be the most ideal one to use though, as it
contains more androgen receptor than most skeletal
muscles (the AR is still less abundant here than in target
tissues such as the ventral prostate).47 48 In integrating
both measures, the anabolic index is used, which relates
the ratio of anabolic to androgenic response for a given
steroid. An anabolic index greater than one indicates a
higher tendency for anabolic effect, and therefore
classifies the drug as an anabolic steroid. A measure lower
than one in turn assesses the steroid as androgenic. There
is some variance between experimental results and the
actual real world experiences with humans, but (with a
few exceptions) designations based on the anabolic index
are generally accepted. Below are discussed a few factors
that greatly affect anabolic/androgenic dissociation.
Nandrolone and 19-norandrogens
The section of this book dealing with DHT conversion is
important, because it helps us understand the anabolic
steroid nandrolone and many of its derivatives.
Nandrolone is identical to testosterone except it lacks a
carbon atom in the 19th position, hence its other given
name 19-nortestosterone. Nandrolone is very interesting
because it offers the greatest ratio of anabolic to
androgenic effect of the three natural steroids (see:
Synthetic AAS Chemistry).This is because it is metabolized
into a less potent structure (dihydronandrolone) in
androgen target tissues with high concentrations of the 5alpha
reductase enzyme, which is the exact opposite of
what happens with testosterone. Apparently the removal
of the c4-5 double bond, which normally increases the
androgen receptor binding capability of testosterone,
causes an unusual lowering of this ability with
nandrolone.lnstead of becoming three to four times more
potent, it becomes several times weaker. This is a very
desirable trait if you want to target anabolic effects over
androgenic. This characteristic also carries over to most
synthetic steroids derived from nandrolone, making this
an attractive base steroid to use in the synthesis of new,
primarily anabolic, steroids.
5-alpha Irreducible Steroids
When we look at the other mild anabolic steroids
Primobolan®, Winstrol®, and Anavar, none of which are
derived from nandrolone, we see another interesting
commonality. These steroids are DHT derivatives that are unaffected by 5alpha-reductase, and therefore become neither weaker nor
stronger in androgen responsive target tissues with high concentrations of this
enzyme. In essence, they have a very balanced effect between muscle and
androgen tissues, making them outwardly less androgenic than testosterone.
This is why these steroids are technically classified as anabolics, and are
undeniably less troublesome than many other steroids in terms of promoting
androgenic side effects. However, if we wanted to look for the absolute least
androgenic steroid, the title would still go to nandrolone (or perhaps one of its
derivatives). Female bodybuilders should likewise take note that despite the
recommendations of others, steroids like Anavar, Winstrol and Primo are not
the least risky steroids to use. This is of great importance, as male sex
hormones can produce many undesirable and permanent side effects when
incorrectly taken by females (See: Side Effects, Virilization).
3-alpha Hydroxysteroid Dehydrogenase
The 3-alpha hydroxysteroid dehydrogenase enzyme is also important,
because it can work to reduce the anabolic potency of certain steroids
considerably. As follows, not all potent binders of the androgen receptor are,
as a rule, great muscle-building drugs, and this enzyme is an important factor.
Dihydrotestosterone is a clear example. Just as the body converts
testosterone to DHT as a way to potentiate its action in certain tissues (skin,
scalp, prostate, etc.), it also has ways of countering the strong activity of
DHT, in other tissues where it is unneeded. This is accomplished by the
rapid reduction of DHT to its inactive active metabolites, namely
androstanediol, before it reaches the androgen receptor. This activity occurs
via interaction with the 3-alpha hydroxysteroid dehydrogenase enzyme. This
enzyme is present in high concentrations in certain tissues, including skeletal
muscle, and DHT is much more open to alteration by it than other steroids
that possess a c4-5 double-bond (like testosterone).49 This causes
dihydrotestosterone to be an extremely poor anabolic, despite the fact that it
actually exhibits a much higher affinity for the cellular androgen receptor than
most other steroids. Were it able to reach the cellular androgen receptor
without first being metabolized by 3a-HSD, it certainly would be a
formidable muscle-building steroid. Unfortunately this is not the case,
explaining why injectable dihydrotestosterone preparations (no longer
commercially produced) were never favorite drugs among athletes looking to
build mass. This trait is also shared by the currently popular oral androgen
Proviron®, which is, in essence, just an oral form of DHT (1-methyldihydrotestosterone to be specific) and known to be an extremely poor tissue
builder.
Anabolics and Potency
One must remember that being classified as an anabolic just means that the
steroid is more inclined to produce muscle growth than androgenic side
effects. Since both effects are mediated through the same receptor, and
growth is not produced by androgen receptor activation in muscle tissue
alone (other CNS tissues, for example, are integral to this process as well),
we find that a reduction in the androgenic activity of a compound will often
coincide with a similar lowering of its muscle-building effectiveness. If we are
just looking at overall muscle growth, androgenic steroids (usually potent due
to their displaying a high affinity to bind with the androgen receptor in all
tissues) are typically much more productive muscle-builders than anabolics,
which usually bind with lower affinity in many tissues. In fact, with all of the
analogues produced throughout the years, the base androgen testosterone is
still considered to be one of the most effective bulking agents. The user must
simply endure more side effects when acquiring his or her new muscle with
this type of drug. Individuals wishing to avoid the stronger steroids will,
therefore, make a trade-off, accepting less overall muscle gain in order to run
a more comfortable cycle.
RBA Assay:
Another way of evaluating the potential ratio of anabolic to androgenic
activity is the practice of comparing the relative binding affinity (RBA) of
various steroids for the androgen receptor in rat skeletal muscle versus
prostate. When we look at the detailed study published in 1984, we see some
recognizable (and expected) trends. Aside from dihydrotestosterone and
Proviron® (mesterolone), which undergo rapid enzymatic reduction in
muscle tissue to inactive metabolites, the remaining anabolic/androgenic
steroids seem to bind with near equal affinity to receptors in both tissues.
They seem to be relatively “balanced” in effect. This study also discusses the
unique activity of testosterone and nandrolone compounds, which are good
substrates for the 5a-reductase enzyme found in androgen target tissues (such
as the prostate), and seem to provide the most notable variance between
anabolic and androgenic effect in humans due to this local metabolism. When
it comes to real-world use in humans, anabolic steroids do not always behave
in 100% uniformity with their anabolic and androgenic profiles as determined
by animal models, so all such figures need to be taken with a small grain of
salt.
